NUCLEAR CONTROL OF CELL GROWTH AND DIFFERENTIATION PROGRAM ABSTRACT The Nuclear Control of Cell Growth and Differentiation (NC) Program is a basic science program that provides innovative approaches that lead to impactful understanding of the mechanistic basis of cancer development. The leadership, membership, and activities combine to achieve a particular aspect of the Huntsman Cancer Institute (HCI) mission statement??to understand cancer from its beginnings.? This is accomplished through experimentation focused on mechanisms underlying basic nuclear processes and pathways that go awry in cancer cells and contribute to oncogenesis. NC members use innovative discovery science and preclinical models for the purpose of dissecting fundamental aspects of cell growth and differentiation that occur in and/or impact the nucleus. Within these broad goals, research in the NC Program pursues three Specific Aims: 1) to decipher the roles of gene dysregulation in cancer; 2) to define relationships between metabolic dysregulation and gene networks in cancer; and 3) to reveal altered mechanisms of DNA damage, replication, and repair in cancer. Each of these three Specific Aims involves the investigation of both normal nuclear processes, as well as their dysregulation in cancer. A deep and fundamental understanding of both states is needed to develop the most effective diagnostics, the best tailored therapies, and the clearest and most effective guidelines related to prevention?in alignment with the mission of HCI. The NC Program has 33 members with academic appointments in 12 University of Utah departments in three schools/colleges. Program members are well funded, with a strongly positive funding trajectory that is increasingly cancer-focused. Peer-reviewed funding totals $11.1M in direct costs, of which $3.9M (35%) derives from the National Cancer Institute. Program members published 329 peer-reviewed papers; 12% represented intra-programmatic efforts and 27% resulted from inter-programmatic collaborations. Twenty- seven percent of publications were in journals with an impact factor greater than 10. As a cancer-focused basic science program, the NC Program has a major positive impact on the Cancer Center through innovation and research excellence in gene regulation, cancer metabolism, and genome stability?as well as enhancing education and training of HCI trainees in these areas. Thus, NC provides discovery science that can be translated to the clinic and population, with special attention to understanding basic mechanisms underlying cancers of high incidence in HCI?s catchment area, including melanoma, lung, breast, and childhood cancers. NC Program members continue to play leading roles in cancer-focused discovery research and partner with colleagues in all four HCI Research Programs for translational impact.